The obese strain (OS) chicken spontaneously develops thyroiditis at an early age. The hypothesis to be tested in the proposal is that the thyroid target organ susceptibility factor in the OS chicken is an abnormal redox equilibrium. This oxidative shift during embryogenesis may result in failure of immune tolerance to thyroid antigens. The six goals to the proposal are to:- 1) Expand preliminary data that OS thyroids have increased sensitivity to oxidant-induced damage. 2) Determine if the OS thyroid contains reduced levels of anti-oxidant factors, including glutathione, glutathione reductase, glutathione peroxidase and catalase. 3) Examine whether there is a relationship between NO levels and the development of thyroiditis. 4) Examine the relationship between thyroiditis and the expression of certain death/viability genes that play a role in apoptosis, including bcl-2/bax and mcl-1/c-rel. They will also overexpress bcl-2 and bax in chick thyroids. 5) Confirm that the abnormalities present after hatching are also present in embryonic thyroids. 6) Design and implement a low iodine regiment that completely prevents embryonic thyroidal iodine uptake and to determine the effect of this manipulation on the induction of disease after hatching.